The side effects of excessive intake of L-arginine and preventive measures

As a semi-essential amino acid, appropriate supplementation of L-Arginine can exert hepatoprotective, immune-regulatory, and microcirculation-improving effects. However, excessive intake (more than 10 g per day, or long-term high-dose supplementation) can disrupt the balance of amino acid metabolism in the body, triggering multi-system side effects. The risks are particularly elevated in populations with hepatic or renal insufficiency and metabolic disorders. Understanding its side effects and preventive measures is a core prerequisite for the safe supplementation of L-Arginine.

I. Main Side Effects of Excessive L-Arginine Intake

Gastrointestinal System Disorders

This is the most common acute side effect of excessive intake, associated with the catabolism of arginine in the intestines and changes in osmotic pressure:

High-dose L-Arginine can be decomposed by intestinal bacteria to produce substances such as ammonia and amines, which irritate the intestinal mucosa and induce symptoms including abdominal distension, abdominal pain, diarrhea, nausea, and vomiting.

Excessive arginine increases the osmotic pressure in the intestinal lumen, causing water outside the intestines to flow into the lumen, exacerbating diarrhea and, in severe cases, leading to dehydration or electrolyte imbalance.

Long-term excessive supplementation may also disrupt the balance of the intestinal flora, inhibit the growth of beneficial bacteria, and further aggravate digestive dysfunction.

Increased Burden on Hepatic and Renal Functions and Metabolic Abnormalities

The liver and kidneys are the core organs for L-Arginine metabolism, and excessive intake directly increases their metabolic pressure:

Hepatic Risks: Under normal circumstances, L-Arginine is catalyzed by arginase in the liver to decompose into urea and ornithine, achieving ammonia clearance. However, excessive intake overloads the hepatic urea cycle, resulting in a transient increase in blood ammonia levels. Particularly in individuals with hepatic insufficiency (e.g., cirrhosis, hepatitis patients), elevated blood ammonia may induce or exacerbate hepatic encephalopathy, manifesting as neurological symptoms such as confusion and behavioral abnormalities. Meanwhile, excessive arginine may interfere with the absorption and metabolism of other amino acids in the liver, disrupting the homeostasis of protein synthesis.

Renal Risks: Metabolites of L-Arginine (e.g., urea, creatinine) need to be excreted through the kidneys. Excessive intake increases the filtration and excretion burden of the kidneys. Long-term high-dose supplementation may cause an elevation in glomerular filtration pressure. In patients with renal insufficiency, it is prone to exacerbating renal damage, characterized by increased urinary protein, and elevated serum creatinine and urea nitrogen levels.

Potential Risks to the Cardiovascular System

Excessive L-Arginine intake can trigger functional disorders of the cardiovascular system through excessive NO production:

At normal doses, NO generated from L-Arginine can dilate blood vessels. However, excessive intake leads to overproduction of NO, which excessively dilates peripheral blood vessels and causes hypotension. Especially in individuals with inherently low blood pressure or those taking antihypertensive drugs, it may induce symptoms such as dizziness, fatigue, and orthostatic hypotension.

Excessive NO can also inhibit platelet aggregation, prolong clotting time, and increase the risk of bleeding. The risk is more significant in populations with bleeding tendencies (e.g., gastric ulcer bleeding, coagulation disorders) or those taking anticoagulant drugs (e.g., warfarin, aspirin).

Metabolic and Endocrine Disorders

Electrolyte Imbalance: Excessive L-Arginine promotes renal excretion of potassium ions during metabolism. Long-term supplementation may lead to hypokalemia, manifesting as muscle weakness, constipation, and arrhythmias.

Fluctuations in Insulin Sensitivity: Although appropriate L-Arginine can improve insulin sensitivity, excessive intake may stimulate excessive insulin secretion, resulting in hypoglycemia. Especially in diabetic patients, it may interfere with blood glucose control.

Amino Acid Antagonism: Excessive L-Arginine competitively inhibits the absorption of other neutral amino acids (e.g., leucine, isoleucine). Long-term excessive intake may lead to branched-chain amino acid deficiency, affecting muscle protein synthesis and immune function.

Allergic and Immune Abnormal Reactions

A small number of people may experience allergic reactions due to excessive L-Arginine intake, such as skin itching, rashes, and urticaria. In severe cases, it can lead to difficulty breathing and laryngeal edema. In addition, excessive arginine may overactivate immune cells, trigger an imbalance in the release of inflammatory factors, and exacerbate the condition of patients with autoimmune diseases.

II. Core Measures to Prevent Side Effects of L-Arginine Overdose

Strictly Control Supplementation Dosage and Follow the Principle of Individualization

Healthy Populations: Daily nutritional supplementation does not require additional intake, as dietary sources (e.g., lean meat, fish, nuts, beans) are sufficient to meet the body’s needs. If supplementation is necessary for special purposes (e.g., post-exercise recovery, microcirculation improvement), the daily dose should be controlled at 3–6 g, and continuous supplementation should not exceed 2 weeks to avoid long-term high-dose use.

Special Populations: Patients with liver diseases need to adjust the dosage under the guidance of a doctor. Individuals with hepatic insufficiency should not exceed 3 g per day, and blood ammonia levels need to be monitored. Patients with kidney diseases should strictly limit the dosage or avoid supplementation. Populations with diabetes, hypertension, or bleeding tendencies should consult a doctor before supplementation to avoid adverse reactions caused by combined use with drugs.

Avoid Blind Stacking: It is not recommended to take multiple supplements containing L-Arginine (e.g., amino acid oral liquids, sports nutrition powders) simultaneously to prevent total dosage exceeding the limit.

Prioritize Natural Food Sources and Reduce Dependence on Artificial Supplements

L-Arginine from natural foods has a balanced ratio with other amino acids, which is less likely to cause metabolic imbalance and is a safer intake method:

Foods rich in L-Arginine include chicken breast, salmon, eggs, soybeans, walnuts, etc. A reasonable daily diet can meet the body’s needs.

Artificial supplements should only be considered when there is a clear arginine deficiency (e.g., severe malnutrition, post-operative recovery period) or on the advice of a doctor.

Administer in Divided Doses to Reduce Gastrointestinal IrritationIf artificial preparations need to be supplemented, it is recommended to divide the daily dose into 2–3 administrations to avoid a single fasting intake. Meanwhile, it can be taken with food to reduce intestinal osmotic pressure stimulation and lower the risk of abdominal distension and diarrhea.

Strengthen Monitoring and Timely Adjust the Supplementation RegimenIndividuals taking long-term L-Arginine supplementation need to regularly monitor hepatic and renal functions (serum creatinine, urea nitrogen, transaminases), electrolytes (serum potassium), and blood ammonia levels. If abnormal indicators appear, supplementation should be stopped immediately and medical advice should be sought.If symptoms such as diarrhea, dizziness, or rashes occur during supplementation, the medication should be discontinued promptly, and medical intervention is required for severe symptoms.

Strictly Avoid High-Dose Supplementation in Contraindicated PopulationsThe following populations should be cautious about supplementation or avoid using L-Arginine supplements:

Individuals with severe hepatic or renal insufficiency (e.g., decompensated cirrhosis, renal failure);

Patients with hypotension, or those taking antihypertensive drugs or anticoagulants;

People with bleeding tendencies or coagulation disorders;

Individuals allergic to L-Arginine;

Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus) in the active phase.

The safe boundary of L-Arginine supplementation lies in appropriateness and individualization. Side effects of excessive intake mostly stem from metabolic overload and amino acid balance disorders, with significantly increased risks for special populations. Side effects can be effectively prevented by controlling the dosage, prioritizing natural foods, and strengthening health monitoring. If high-dose supplementation is required for medical purposes, it must be conducted under the guidance of a professional doctor to avoid health risks caused by self-medication.